A. The perineurium of frog sciatic nerve, which regulates nerve function, contains concentric cell layers that act as a diffusion barrier because of the presence of tight junctions. The cells have vesicles which take up extracellular lanthanum but do not form complete transcellular channels. Perineurial permeability is low to ions and water-soluble nonelectrolytes, but high to lipid soluble nonelectrolytes. There is evidence of active ion transport. The hydrostatic pressure in the nerve is positive and reflects the role of the perineurium as an osmotically active membrane. Nerve capillaries form part of a blood-nerve barrier. B. Fatigue of single frog muscle fibers appears as a decline in tension output during prolonged tetanic stimulation. The concentration of adenosinetriphosphate (ATP) (an energy source for contraction) remained normal in fatigued fibers. Furthermore, ATP was not available for contraction, because it could be consumed during caffeine-induced contractures. We suggest that H+, as lactic acid, accumulates in fatigued fibers and interferes with excitation-contraction coupling.